Analysis of gene function at the molecular. cellular and organismic level requires the availability of diverse sophisticated analytic tools. The Jackson Laboratory (TJL) is making major contributions in the area of mammalian genetics with active research programs and vast resources of mouse models and bio-informatic databases. The success of a majority of these programs relies heavily on state-of-the-art equipment to facilitate imaging at finer and more quantitative levels to follow the minute changes a single gene may cause. It is critical that the research programs of TJL have access to this level of technology to allow expansion of the research to new levels of resolution and therefore, understanding. The Jackson Laboratory proposes to incorporate the requested Leica TCS 4D Confocal Microscopy System integrated with the Leica DMRE Upright Microscope, into a network of research and resource programs aimed at developing and analyzing mouse models of human diseases. Presently, there is no similar state-of-the-art system available to researchers at TJL or in this area of the state. Researchers at TJL desperately need access to a state-of-the-art confocal microscope and the ability to render those images as 3D reconstructions. The currently available. mercury-source fluorescence microscope, is inadequate to specifically localize fluorescent probes at the required resolution, and render the data in a format providing the necessary dimensional information. The equipment requested in this application was selected by an active scientific advisory committee specifically to encompass all the current and foreseeable needs of the Scientific Staff at TJL that are not able to be met through traditional funding mechanisms. It will be maintained and utilized to the limits of its technology in a core of centralized Shared Scientific Services that have produced quality research at TJL for over 30 years. The system requested will expand the boundaries currently set by the limitations of our current technology, and bring us into the twenty-first century.